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解析体外扩增 γδ T 细胞的细胞组分以优化神经母细胞瘤免疫治疗试验中强效细胞治疗供者的选择

英文原题:Dissecting the cellular components of ex vivo γδ T cell expansions to optimize selection of potent cell therapy donors for neuroblastoma immunotherapy trials.

PubMed 2022/03/26(内容时间) Oncoimmunology Q1 · IF 6.2(JCR 2025)

研究概要

这些研究共同凸显了在扩增的 T 细胞疗法中保留 NK 细胞群体的价值,并提示固有免疫细胞联合免疫治疗对神经母细胞瘤具有协同作用。

中文摘要

T淋巴细胞是一类新兴的细胞免疫疗法,临床前研究显示其有望用于癌症治疗,尤其是神经母细胞瘤。γδ T细胞具有类似先天免疫的特性,可不依赖主要组织相容性复合体(MHC)识别而天然杀伤肿瘤细胞,因此可采用健康供者来源的异基因T细胞疗法。目前的一个局限是,不同个体的白细胞采集物在T细胞扩增能力上差异显著。克服这一问题有助于充分发挥异基因T细胞疗法的潜力。本研究分析了健康成年供者来源的T细胞扩增情况,发现唑来膦酸和IL-2刺激时,具有较强效应活性的自然杀伤(NK)淋巴细胞也会随T细胞一同扩增。NK细胞的存在与T细胞扩增潜力及T细胞疗法的总体效力均相关。然而,细胞疗法与抗体类免疫治疗药物地努图昔单抗联用时,其效力似乎不受T/NK细胞含量影响,无论体外还是体内实验均如此;这减轻了个体间扩增差异对疗效的影响。总体而言,这些研究凸显了在扩增的T细胞疗法中保留NK细胞群的价值,并提示联合先天免疫细胞疗法可能对神经母细胞瘤产生协同作用。

展开英文摘要原文

T lymphocytes represent an emerging class of cellular immunotherapy with preclinical promise to treat cancer, notably neuroblastoma. The innate-like immune cell subset demonstrates inherent cytoxicity toward tumor cells independent of MHC recognition, enabling allogeneic administration of healthy donor-derived T cell therapies. A current limitation is the substantial interindividual T cell expansion variation among leukocyte collections. Overcoming this limitation will enable realization of the full potential of allogeneic T-based cellular therapy. Here, we characterize T cell expansions from healthy adult donors and observe that highly potent natural killer (NK) lymphocytes expand with T cells under zoledronate and IL-2 stimulation. The presence of NK cells correlates with both the expansion potential of T cells and the overall potency of the T cell therapy. However, the potency of the cell therapy in combination with an antibody-based immunotherapeutic, dinutuximab, appears to be independent of T/NK cell content both in vitro and in vivo , which minimizes the implication of interindividual expansion differences toward efficacy. Collectively, these studies highlight the utility of maintaining the NK cell population within expanded T cell therapies and suggest a synergistic action of combined innate cell immunotherapy toward neuroblastoma.

论文信息

作者
Jonus HC、Burnham RE、Ho A、Pilgrim AA、Shim J、Doering CB、Spencer HT、Goldsmith KC
单位
Department of Pediatrics, Aflac Cancer and Blood Disorders Center, Emory University School of Medicine, Atlanta, GA, USA.United States
文献类型
美国 NIH 资助研究 · 非美国政府资助研究
期刊
Oncoimmunology2022
原文标识
PubMed 35371623 · DOI 10.1080/2162402X.2022.2057012